The present invention relates to compositions which intend to control the concentration of serum remnant-like lipoproteins. In detail, the present invention relates to serum remnant-like lipoprotein concentration regulators which can control increase oft he concentration of human serum remnant-like lipoproteins in safety and to the appropriate range; foods for controlling the concentration of serum remnant-like lipoproteins which contain the serum remnant-like lipoprotein concentration regulators; and pharmaceutical compositions for controlling the concentration of serum remnant-like lipoproteins.
Serum remnant-like lipoproteins are usually transitory intermediate metabolites which are produced by hydrolysis of lipoproteins such as chylomicron lipoproteins (CM) of intestinal origin and very low density lipoproteins (VLDL) of hepatic origin, which are rich in neutral fat, by lipoprotein lipase. The former is referred to as CM remnants and the latter is referred to as VLDL remnants. Both remnant-like lipoproteins are relatively rich in cholesterol. Though those serum remnant-like lipoproteins are usually metabolized immediately and exist little in bodies of healthy people which are hungry in the early morning, they persist in the blood and increase when metabolizing process thereof is impaired. As a typical case of so-called hyper remnant lipoproteinemia which is induced by persistence of remnant-like lipoproteins in the blood, type III familial hyperlipidemia is known, wherein metabolism of serum remnant-like lipoproteins is impaired and the serum remnant-like lipoproteins become in stasis and accumulate. In addition, since serum remnant-like lipoproteins have relatively high cholesterol content among triglyceride-rich lipoproteins, they are easily ingested into vessel walls. As a result, cholesterol in serum remnant-like lipoproteins is easily accumulated in vessel walls. Further, as serum remnant-like lipoproteins are ingested into a macrophage and convert the macrophage into foam cells which are incipient lesion of arterial sclerosis (Mahley R. W., “Atherogenic lipoproteins and coronary artery disease: concepts derived from recent advances in cellular and molecular biology”, Circulation (U.S.A.), vol. 72, No. 5, 943-948, 1985, and Kosaka S. et al., “Evidence of macrophage foam cell formation by very low-density lipoprotein receptor”, Circulation (U.S.A.), vol. 103, No. 8, 1142-1147, 2001), serum remnant-like lipoproteins which increase in the blood though eating are paid attention to as a risk factor of onset of arterial sclerosis. Since human have many opportunities to eat between meals besides three meals a day, it is thought that they are in a postprandial state rather than on an empty stomach a lot of time of the day. Thus, importance of research on postprandial hyperlipidemia (that is, hyperlipidemia which shows abnormal amplification of serum lipids after eating though one is in normolipemic status when he/she is hungry in the early morning, or shows persistence of amplification thereof) has been emphasized for recent years, while previously questioned was a level of serum lipids which was calculated based on the blood collected on an empty stomach. In postprandial hyperlipidemia, CM and CM remnants constitute major part of serum lipids, and CM remnants' evoking of arterial sclerosis has been pointed out for a while (Zilversmit D. B., “Atherogenesis: a post-prandial phenomenon”, Circulation (U.S.A.), vol. 60, No. 3, 473-485, 1979, and Karpe F et al., “Postprandial lipoproteins and progression of coronary atherosclerosis”, Atherosclerosis (Netherlands), vol. 106, No. 1, 83-97, 1994). Therefore, it is very important in terms of preventing onset of arterial sclerosis and treatment after onset thereof that serum remnant-like lipoproteins are made reduced. Since improvement of daily diet occupies an important place in preventing onset of arterial sclerosis, there are desired those which can be easily ingested in everyday life, lower postprandial serum remnant-like lipoproteins and be used without concerning about side effects.
Conventionally, quantity of serum remnant-like lipoproteins is determined by immunosorbent assay. Immunosorbent assay is a commonly used method as analysis method of serum remnant-like lipoprotein and is carried out by determination of cholesterol contained in serum remnant-like lipoprotein (hereinafter referred to as serum RLP-cholesterol) as a value reflecting serum remnant-like lipoproteins. For details, it is the analysis method comprising steps of adding samples to suspension of a buffer and an insoluble support to which anti-human apo A-I and apo B-100 monoclonal antibodies are immobilized, slowly mixing by shaking and standing still; adding a enzyme reagent(s) which reacts to cholesterol part in serum remnant-like lipoproteins to a supernatant fluid containing serum remnant-like lipoproteins which did not react with the antibodies; and determining the amount of cholesterol in the supernatant fluid (Nakajima K. et al., “Cholesterol in remnant-like lipoproteins in human serum using monoclonal anti apo B-100 and anti apo A-I immunoaffinity mixed gels”, Clin Chim Acta (Netherlands), vol. 223, Nos. 1 and 2, 53-71, 1993). Among apo proteins existing in serum, CM and high density lipoproteins (HDL) have apo A-I, and VLDL and low density lipoproteins (LDL) have apo B-100. They bond with each of antibodies to precipitate, and remnant-like lipoproteins (CM remnants and VLDL remnants) exist as nonbonding fractions in supernatant fluid thereof. The cholesterol value in these fractions is regarded as that reflecting remnant-like lipoproteins and determined clinically in our country.
Medium-chain triglyceride (triglyceride of medium-chain fatty acids) has been used as solvents for oil-soluble flavoring/coloring agents for food; mold release/lubricating oils for food; or pharmaceutical raw materials because it has high oxidation stability, low freezing point and viscosity, high solubility and it is also transparent and colorless. Further, as medium-chain triglyceride has high absorbability and energy proportion thereof are higher than that of sugar groups, it has also been used as raw materials of enteral nutrients, wherein efficient energy supplementation is intended.
It has also been reported that controlling effect of postprandial neutral fat concentration in the blood (inhibiting effect on elevation thereof) is brought by replacing dietary fat and oil with medium-chain triglyceride (Calabrese, C. et al., “A cross-over study of the effects of a single oral feeding of medium chain triglyceride oil vs. canola oil on post-ingestion plasma triglyceride levels in healthy men”, Alternative Medicine Review (U.S.A.), vol. 4, No. 1, 23-28, 1999). However, it has not yet been discovered that medium-chain triglyceride has inhibiting function on elevation of the concentration of serum remnant-like lipoproteins.